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Osteopontin as Novel Prognostic Biomarker for Heart Failure

a biomarker and heart failure technology, applied in biochemistry equipment and processes, instruments, material analysis, etc., can solve the problems of significant morbidity and mortality, heart failure, etc., and achieve the effect of improving the non-invasive monitoring of right ventricular dysfunction and remodelling

Inactive Publication Date: 2010-10-21
UNIVERSITATSKLINIKUM HEIDELBERG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0096]Preferably there are inclusion criteria for the first subgroup (subjects with heart failure): minimum age, such as 18 years; medication, such as ACE inhibitor or angiotensin II receptor blocker; significantly reduced left ventricular systolic function, such as with an ejection fraction of less than 40%.
[0209]For details, see Example 3, which shows for the first time that plasma levels of OPN are elevated in patients with chronic pulmonary arterial hypertension. Therefore, the novel biomarker OPN can improve the non invasive monitoring of right ventricular dysfunction and remodelling in patients with PAH. (see also FIGS. 9 to 13).

Problems solved by technology

Heart failure is a highly prevalent syndrome throughout the industrialized world, associated with significant morbidity and mortality.

Method used

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  • Osteopontin as Novel Prognostic Biomarker for Heart Failure
  • Osteopontin as Novel Prognostic Biomarker for Heart Failure
  • Osteopontin as Novel Prognostic Biomarker for Heart Failure

Examples

Experimental program
Comparison scheme
Effect test

example 1

Methods

1. Study Population

a) Heart Failure Patients

[0232]Heart failure patients were recruited from the specialized heart failure clinic of a large university hospital that serves as a tertiary referral center in southern Germany. Eligible patients were ≧18 years of age and revealed significantly reduced left ventricular systolic function with an ejection fraction of less than 40%. Patients with dilated cardiomyopathy or ischemic heart failure were both included. Because Angiotensin II extensively stimulates osteopontin expression in the heart, all patients had to be taking an ACE-Inhibitor or Angiotensin II receptor blocker. All examinees enrolled in the present study had to have been taking stable medication one month before inclusion. Patients with malignant or inflammatory diseases, history of organ transplantation and significant acute / chronic renal failure (serum creatinine>2 mg / dl) were excluded.

[0233]According to the in- and exclusion criteria we performed a database inquiry...

example 2

Results

Clinical Characteristics of Patient Cohort and Control Subjects

[0244]Among 420 patients 267 had dilated cardiomyopathy (64%) and 153 an ischemic origin of heart failure (36%). The median age of the heart failure group was 57 years and included 342 men (81%) and 78 women (19%). The control group was comprised of 17 men (39.5%) and 26 women (60.5%) with a median age of 59 years.

[0245]The distribution of cardiovascular risk factors was similar in heart failure patients and controls (see Table 7 below).

Osteopontin Plasma Levels are Significantly Increased in Patients with Heart Failure-Irrespective of the Underlying Etiology

[0246]The median osteopontin plasma level in the control sample was 382 ng / ml (interquartile range: 257 ng / ml-540 ng / ml). Patients with systolic heart failure displayed a significantly higher (p=0.008) median osteopontin plasma level of 532 ng / ml (232 ng / ml-875 ng / ml). The upregulation of osteopontin plasma levels was independent of the underlying heart failur...

example 3

Osteopontin Plasma Level Independently Predict Right Ventricular Dysfunction in Patients with Pulmonary Arterial Hypertension

[0260]The extracellular matrix protein Osteopontin (OPN) was found upregulated in several models of cardiac failure and appears to play an important role in myocardial remodeling. Moreover, the inventors showed herein that OPN plasma level are not only elevated in patients with left sided heart failure, but also correlated with an adverse prognosis. Since right ventricular dysfunction is an important predictor of morbidity and mortality in patients with pulmonary arterial hypertension (PAH), we now assessed the diagnostic power of OPN in this patient cohort.

[0261]We included 85 patients with PAH of different etiology in this study, while 43 healthy individuals of similar age and sex distribution served as controls. OPN plasma levels were determined by ELISA and assessed for correlation with clinical severity, echocardiographic parameters of right ventricular d...

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Abstract

The present invention relates to methods for providing a diagnosis, prognosis and / or risk stratification of a subject with heart failure, comprising determining the concentration of osteopontin (OPN) in the biological sample, preferably in a plasma sample. An OPN cut-off value is discloses as a valuable reference value. The present invention furthermore relates to the use of osteopontin as marker for diagnosis, prognosis and / or risk stratification of a subject with heart failure, the use of the determination of the osteopontin plasma concentration in a biological sample of a subject for diagnosis, prognosis and / or risk stratification of heart failure as well as kits for performing the methods and uses of the invention. The present invention allows particularly for risk stratification of patients with heart failure, such as mortality prediction and prognosis of heart failure severity.

Description

[0001]The present invention relates to methods for providing a diagnosis, prognosis and / or risk stratification of a subject with heart failure, comprising determining the concentration of osteopontin (OPN) in the biological sample, preferably in a plasma sample. An OPN cut-off value is discloses as a valuable reference value. The present invention furthermore relates to the use of osteopontin as marker for diagnosis, prognosis and / or risk stratification of a subject with heart failure, the use of the determination of the osteopontin plasma concentration in a biological sample of a subject for diagnosis, prognosis and / or risk stratification of heart failure as well as kits for performing the methods and uses of the invention. The present invention allows particularly for risk stratification of patients with heart failure, such as mortality prediction and prognosis of heart failure severity.BACKGROUND OF THE INVENTION[0002]Heart failure is a highly prevalent syndrome throughout the in...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/53C12Q1/02G01N33/48G01N33/58
CPCG01N2800/325G01N33/6887
Inventor FREY, NORBERTROSENBERG, MARKKATUS, HUGO
Owner UNIVERSITATSKLINIKUM HEIDELBERG
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